We propose to study the effect of starvation on the metabolism of thyroid hormone and the way in which the alterations in thyroid hormone metabolism affect the metabolic response to starvation. We will determine if the decline in triiodothyronine in starvation brings about a hypothyroid state and the extent to which such a hypothyroid state might account for the metabolic adaptations which occur in starvation. We will study the metabolic signals which influence the peripheral conversion of T4 to T3 and other metabolites. Normal or obese volunteers will be studied during fasting periods with or without thyroid hormone replacement. We will measure clinical parameters of thyroid status including the basal metabolic rate and the excretion of metabolites of androgens and astrogens known to be influenced by thyroid hormone. We will study the nitrogen metabolism of subjects during starvation, and evaluate the effect of thyroid hormone in conservation of protein. A variety of hormones and substrates will be tested to determine if any of these act as metabolic signals influencing the metabolism of thyroid hormone during starvation.